tbuckley/cabot-search huggingface dataset:
Early vs Deferred Non–Messenger RNA COVID-19 Vaccination Among Chinese Patients With a History of Inactive Uveitis
Authors: Zhenyu Zhong, Qiuying Wu, Yuxian Lai, Lingyu Dai, Yu Gao, Weiting Liao, Guannan Su, Yao Wang, Chunjiang Zhou, Peizeng Yang
Journal: JAMA Network Open (2023)

Importance Improper host response to COVID-19 vaccines could trigger immune-mediated adverse events. The question remains whether COVID-19 vaccination should be postponed until complete remission in patients with uveitis, a preexisting immune-related condition. Objective To compare recommendations for early and deferred COVID-19 vaccination with respect to uveitis outcomes. Design, Setting, and Participants This open-label, randomized clinical trial at a large, specialized teaching center for uveitis care in China enrolled unvaccinated patients with inactive uveitis between August 10, 2021, and February 22, 2022, with follow-up to June 6, 2022. Interventions Participants were randomly assigned to receive recommendation for early or deferred COVID-19 vaccination after complete remission of uveitis. Non–messenger RNA (non-mRNA) COVID-19 vaccines were available in China during the trial. Main Outcomes and Measures The primary outcome was the time to symptomatic uveitis worsening during 3 months of follow-up. Secondary outcomes included uveitis activity and best-corrected visual acuity at 3 months. Results Of the 543 participants (304 women [56.0%]; median age, 35 [IQR, 26-49] years), 262 were recommended for early vaccination and 281 for deferred vaccination. By month 3, 109 patients (41.6%) in the early group had been vaccinated compared with 14 (5.0%) in the deferred recommendation group. In the intention-to-treat population, the time to symptomatic uveitis worsening was shorter in the early group than in the deferred group (hazard ratio, 1.68 [95% CI, 1.09-2.59]; P = .01 by log-rank test). Changes in anterior chamber cells, vitreous haze, and best-corrected visual acuity from baseline to month 3 appeared similar in the 2 groups in the evaluable population after the month 3 in-person visit. Conclusions and Relevance In this randomized clinical trial of patients with inactive uveitis, recommendation for early non-mRNA COVID-19 vaccination resulted in a higher incidence of self-reported symptomatic uveitis worsening with possible reporting bias compared with recommendation for deferred vaccination, but no adverse effects were observed in disease and visual prognosis at 3 months. These findings would be useful to guide the individual timing choices of non-mRNA COVID-19 vaccination in this clinically vulnerable population. Trial Registration Chinese Clinical Trial Registry: ChiCTR2100049467
Beautiful Noise
Authors: Rafael Campo
Journal: JAMA (2023)

Occasionally it sounds like a cathedral tower full of bells but usually it's more like the last scatter of cicadas at the end of summer, an almost pleasant buzz and whirr, though with a slightly higher pitch, as at night once the light has gone and daytime noise has faded.Crescendos rise then fall in soft waves and reverberate like the keening voices in Ligeti's Lux Aeterna lift and drop, pierce and penetrate, throb and smooth and finally come to rest.
The 25th Anniversary of the American Society of Clinical Investigation’s Korsmeyer Award
Authors: Benjamin D. Humphreys
Journal: Journal of Clinical Investigation (2023)

Investigation (ASCI) presents the Stanley J. Korsmeyer Award to one or two scientists who have made substantial contributions to our understanding of disease and to mentoring the next generation of physician-scientists each year.Originally named the ASCI Award, it was renamed in 2006 to honor the first recipient of the prize, Dr. Stanley J. Korsmeyer (Figure 1), a physician-scientist respected widely for both his impactful science and his own remarkable legacy of mentorship.To recognize
Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) Mitigates Damaging of Hypertensive Nephropathy
Authors: Ying Zhang, Naijin Zhang, Yuanming Zou, Chunyu Song, Kexin Cao, Boquan Wu, Shilong You, Saien Lu, Dong Wang, Jiaqi Xu, Xinyue Huang, Pengyu Zhang, Zihao Fan, Jingwei Liu, Zhongyi Cheng, Zhe Zhang, Chuize Kong, Liu Cao, Yingxian Sun
Journal: Circulation Research (2023)

Hypertension can lead to podocyte damage and subsequent apoptosis, eventually resulting in glomerulosclerosis. Although alleviating podocyte apoptosis has clinical significance for the treatment of hypertensive nephropathy, an effective therapeutic target has not yet been identified. The function of septin4, a proapoptotic protein and an important marker of organ damage, is regulated by post-translational modification. However, the exact role of septin4 in regulating podocyte apoptosis and its connection to hypertensive renal damage remains unclear. We investigated the function and mechanism of septin4 in hypertensive nephropathy to discover a theoretical basis for targeted treatment. Mouse models including Rosa 26 (Gt(ROSA)26Sor)-SIRT2 (silent mating type information regulation 2 homolog-2)-Flag-TG (transgenic) (SIRT2-TG) mice SIRT2-knockout, and septin4-K174Q mutant mice, combined with proteomic and acetyl proteomics analysis, followed by multiple molecular biological methodologies, were used to demonstrate mechanisms of SIRT2-mediated deacetylation of septin4-K174 in hypertensive nephropathy. Using transgenic septin4-K174Q mutant mice treated with the antioxidant Tempol, we found that hyperacetylation of the K174 site of septin4 exacerbates Ang II (angiotensin II)- induced hypertensive renal injury resulting from oxidative stress. Proteomics and Western blotting assays indicated that septin4-K174Q activates the cleaved-PARP1 (poly [ADP-ribose] polymerase family, member 1)-cleaved-caspase3 pathway. In septin4-knockdown human renal podocytes, septin4-K174R, which mimics deacetylation at K174, rescues podocyte apoptosis induced by Ang II. Immunoprecipitation and mass spectrometry analyses identified SIRT2 as a deacetylase that interacts with the septin4 GTPase domain and deacetylates septin4-K174. In Sirt2-deficient mice and SIRT2-knockdown renal podocytes, septin4-K174 remains hyperacetylated and exacerbates hypertensive renal injury. By contrast, in Rosa26-Sirt2-Flag (SIRT2-TG) mice and SIRT2-knockdown renal podocytes reexpressing wild-type SIRT2, septin4-K174 is hypoacetylated and mitigates hypertensive renal injury. Septin4, when activated through acetylation of K174 (K174Q), promotes hypertensive renal injury. Septin4-K174R, which mimics deacetylation by SIRT2, inhibits the cleaved-PARP1-cleaved-caspase3 pathway. Septin4-K174R acts as a renal protective factor, mitigating Ang II-induced hypertensive renal injury. These findings indicate that septin4-K174 is a potential therapeutic target for the treatment of hypertensive renal injury.
Neutrophil Conversion to a Tumor-Killing Phenotype Underpins Effective Microbial Therapy
Authors: Andrew O. Yam, Jacqueline Bailey, Francis Lin, Arnolda Jakovija, Scott E. Youlten, Claudio Counoupas, Matthias Gunzer, Tobias Bald, Trent M. Woodruff, James A. Triccas, Leonard D. Goldstein, David Gallego-Ortega, Shane T. Grey, Tatyana Chtanova
Journal: Cancer Research (2023)

Abstract The inflammatory microenvironment of solid tumors creates a protumorigenic milieu that resembles chronic inflammation akin to a subverted wound healing response. Here, we investigated the effect of converting the tumor microenvironment from a chronically inflamed state to one of acute microbial inflammation by injecting microbial bioparticles directly into tumors. Intratumoral microbial bioparticle injection led to rapid and dramatic changes in the tumor immune composition, the most striking of which was a substantial increase in the presence of activated neutrophils. In situ photoconversion and intravital microscopy indicated that tumor neutrophils transiently switched from sessile producers of VEGF to highly motile neutrophils that clustered to make neutrophil-rich domains in the tumor. The neutrophil clusters remodeled tumor tissue and repressed tumor growth. Single-cell transcriptional analysis of microbe-stimulated neutrophils showed a profound shift in gene expression towards heightened activation and antimicrobial effector function. Microbe-activated neutrophils also upregulated chemokines known to regulate neutrophil and CD8+ T-cell recruitment. Microbial therapy also boosted CD8+ T-cell function and enhanced the therapeutic benefit of checkpoint inhibitor therapy in tumor-bearing mice and provided protection in a model of tumor recurrence. These data indicate that one of the major effector mechanisms of microbial therapy is the conversion of tumor neutrophils from a wound healing to an acutely activated cytotoxic phenotype, highlighting a rationale for broader deployment of microbial therapy in the treatment of solid cancers. Significance: Intratumoral injection of microbial bioparticles stimulates neutrophil antitumor functions, suggesting pathways for optimizing efficacy of microbial therapies and paving the way for their broader utilization in the clinic.
Discriminative Accuracy of the CAPTURE Tool for Identifying Chronic Obstructive Pulmonary Disease in US Primary Care Settings
Authors: Fernando J. Martinez, MeiLan K. Han, Camden Lopez, Susan Murray, David Mannino, Stacey Anderson, Randall Brown, Rowena Dolor, Nancy Elder, Min Joo, Irfan Khan, Lyndee M. Knox, Catherine Meldrum, Elizabeth Peters, Cathie Spino, Hazel Tapp, Byron Thomashow, Linda Zittleman, Barry Make, Barbara P. Yawn, Emily White, Cathy Scott, Megan Urbin, Jeffrey Holtzman, Alicia Morris, Anna Smyth, Stefan Jhagroo, Michelle LoPiccolo, Pete Amari, Claudya Greig, Brandon Holmes, Elisha Malanga, Sergio Martinez, Gretchen McCreary, Cara Pasquale, Linda Walsh, Ruth Tal-Singer, Malin Fagerås, Norbert Feigler, Angus Hamblin, Frank Trudo, Erin Tomaszewski, Alberto de la Hoz, Carl Abbott, Shahin Sanjar, Carlos Tafur, Carole Catapano, Kim Gilchrist, Nancy Kline Leidy, Lindsey Amendola, Jose Flores, Grace Ruh, Tammy Harvey, Ashleigh Skipper, Kate Walsh, Lauren Warsocki, Abm Shafayet, Cynthia Pinargotte, Melba Ventuera, Vikash Mandania, Donna Green, Luis Paredas, Erika Barba, Erica Mezzasalma, Lindsey Williams, Jack Westfall, Jen Ancona, Lori Jarell, Megan Kaiser, Christin Sutter, Ranee Chatterjee, Chad Harrell, Taylor Harris, Kimberly Leathers, Beth Mancuso-Mills, Morgan Mangum, Nikita Shah, Bertha Leon, Matthew Leon, Patty Dionicio, Lindsay Shade, Rebecca Beasley, Andrea Price, Cody Oliver, Christy Flynn, Stephen Greenberg, Lindsay Lowe, Laura McAllister, Rina Leonidas, Katherine O’Hare, Kelsey Strout, Jeremy Thomas, Lyle J. Fagnan, Xaviera Martinez-Armenta, Lindsay Shankle, Martha Snow, Valeria Vazquez-Trejo, Lisa Tannikula, Ariel Leifer, Jonathan Radosta, Kyungran Shim, Christina Wells, Diane Garcia, Samantha Madrid, Esther Pacheco, Leonard Romo, Sara Ross, Evelyn Velazquez, Natasha Brown, Gordon Bernard, Deborah Barnbaum, Joao de Andrade, Daren Knoel, Peter Lindenauer, Andre Rogatko, Marinella Temprosa
Journal: JAMA (2023)

Chronic obstructive pulmonary disease (COPD) is underdiagnosed in primary care.
Tracking All Injuries From Firearms in the US—Reply
Authors: Elinore J. Kaufman, M. Kit Delgado
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
How to move a “fried egg”: membrane blebbing in oligodendrogliomas
Authors: Simone P Niclou, Anna Golebiewska
Journal: Neuro-Oncology (2023)

Journal Article How to move a “fried egg”: membrane blebbing in oligodendrogliomas Get access Simone P Niclou, Simone P Niclou NORLUX Neuro-Oncology Laboratory, Department of Cancer Research, Luxembourg Institute of Health, L-1210, Luxembourg, Luxembourg Corresponding Author: NORLUX Neuro-Oncology Laboratory, Department of Cancer Research, Luxembourg Institute of Health, L-1210, Luxembourg, Luxembourg (simone.niclou@lih.lu). https://orcid.org/0000-0002-3417-9534 Search for other works by this author on: Oxford Academic PubMed Google Scholar Anna Golebiewska Anna Golebiewska NORLUX Neuro-Oncology Laboratory, Department of Cancer Research, Luxembourg Institute of Health, L-1210, Luxembourg, Luxembourg https://orcid.org/0000-0002-4160-2521 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 6, June 2023, Pages 1044–1046, https://doi.org/10.1093/neuonc/noad039 Published: 14 February 2023 Article history Published: 14 February 2023 Corrected and typeset: 06 March 2023
Approaches to Prevention of Firearm Violence—Reply
Authors: Marian E. Betz, Joseph A. Simonetti
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Revisiting checkpoint inhibitors for myeloma: maintenance after stem cell transplant
Authors: Erin W. Meermeier, P. Leif Bergsagel
Journal: Journal of Clinical Investigation (2023)

Multiple myeloma is a hematologic malignancy of plasma cells that manifests with bone marrow tumors causing lytic bone lesions. Autologous stem cell transplantation (ASCT) after high-dose chemotherapy and followed by prolonged maintenance therapy with lenalidomide (LEN) is an effective standard-of-care therapy for multiple myeloma. However, most patients ultimately relapse. Rational combination strategies that address immune dysfunction may prolong the durability of ASCT. In this issue of the JCI, Minnie and colleagues investigated the addition of a checkpoint inhibitor to LEN maintenance therapy after ASCT. They found that the immune checkpoint TIGIT was an optimal target in patient samples. In a syngeneic, immunocompetent multiple myeloma mouse model, blockade of TIGIT synergized with LEN maintenance by inducing immune protection, characterized in part by the expansion of polyfunctional T cells in the bone marrow. The treatment enhanced durable antimyeloma efficacy and has translatable implications.
Tracking All Injuries From Firearms in the US
Authors: Nicole Cook, Marion Sills
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Dectin-1 Acts as a Non-Classical Receptor of Ang II to Induce Cardiac Remodeling
Authors: Shiju Ye, He Huang, Xue Han, Wu Luo, Lili Wu, Yang Ye, Yingchao Gong, Xia Zhao, Weijian Huang, Yi Wang, Xiaohong Long, Guosheng Fu, Guang Liang
Journal: Circulation Research (2023)

Cardiac remodeling in heart failure involves macrophage-mediated immune responses. Recent studies have shown that a PRR (pattern recognition receptor) called dectin-1, expressed on macrophages, mediates proinflammatory responses. Whether dectin-1 plays a role in pathological cardiac remodeling is unknown. Here, we identified a potential role of dectin-1 in this disease.To model aberrant cardiac remodeling, we utilized mouse models of chronic Ang II (angiotensin II) infusion. In this model, we assessed the potential role of dectin-1 through using D1KO (dectin-1 knockout) mice and bone marrow transplantation chimeric mice. We then used cellular and molecular assays to discover the underlying mechanisms of dectin-1 function.We found that macrophage dectin-1 is elevated in mouse heart tissues following chronic Ang II administration. D1KO mice were significantly protected against Ang II-induced cardiac dysfunction, hypertrophy, fibrosis, inflammatory responses, and macrophage infiltration. Further bone marrow transplantation studies showed that dectin-1 deficiency in bone marrow-derived cells prevented Ang II-induced cardiac inflammation and dysfunction. Through detailed molecular studies, we show that Ang II binds directly to dectin-1, causing dectin-1 homodimerization and activating the downstream Syk (spleen tyrosine kinase)/NF-κB (nuclear factor kappa B) signaling pathway to induce expression of inflammatory and chemoattractant factors. Mutagenesis studies identified R184 in the C-type lectin domain to interact with Ang II. Blocking dectin-1 in macrophages suppresses Ang II-induced inflammatory mediators and subsequent intercellular cross talk with cardiomyocytes and fibroblasts.Our study has discovered dectin-1 as a new nonclassical receptor of Ang II and a key player in cardiac remolding and dysfunction. These studies suggest that dectin-1 may be a new target for treating hypertension-related heart failure.
Vital Statistics in Prognosis
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults
Authors: Kristen W. Cohen, Andrew Fiore-Gartland, Stephen R. Walsh, Karina Yusim, Nicole Frahm, Marnie L. Elizaga, Janine Maenza, Hyman Scott, Kenneth H. Mayer, Paul A. Goepfert, Srilatha Edupuganti, Giuseppe Pantaleo, Julia Hutter, Daryl E. Morris, Stephen C. De Rosa, Daniel E. Geraghty, Merlin L. Robb, Nelson L. Michael, Will Fischer, Elena E. Giorgi, Harmandeep Malhi, Michael N. Pensiero, Guido Ferrari, Georgia D. Tomaras, David C. Montefiori, Peter B. Gilbert, M. Juliana McElrath, Barton F. Haynes, Bette T. Korber, Lindsey R. Baden
Journal: Journal of Clinical Investigation (2023)

BACKGROUNDMosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models.METHODSThis double-blind randomized trial enrolled 105 healthy HIV-uninfected adults who received 3 doses of either a trivalent global mosaic, a group M consensus (CON-S), or a natural clade B (Nat-B) gp160 env DNA vaccine followed by 2 doses of a heterologous modified vaccinia Ankara-vectored HIV-1 vaccine or placebo. We performed prespecified blinded immunogenicity analyses at day 70 and day 238 after the first immunization. T cell responses to vaccine antigens and 5 heterologous Env variants were fully mapped.RESULTSEnv-specific CD4+ T cell responses were induced in 71% of the mosaic vaccine recipients versus 48% of the CON-S recipients and 48% of the natural Env recipients. The mean number of T cell epitopes recognized was 2.5 (95% CI, 1.2-4.2) for mosaic recipients, 1.6 (95% CI, 0.82-2.6) for CON-S recipients, and 1.1 (95% CI, 0.62-1.71) for Nat-B recipients. Mean breadth was significantly greater in the mosaic group than in the Nat-B group using overall (P = 0.014), prime-matched (P = 0.002), heterologous (P = 0.046), and boost-matched (P = 0.009) measures. Overall T cell breadth was largely due to Env-specific CD4+ T cell responses.CONCLUSIONPriming with a mosaic antigen significantly increased the number of epitopes recognized by Env-specific T cells and enabled more, albeit still limited, cross-recognition of heterologous variants. Mosaic and consensus immunogens are promising approaches to address global diversity of HIV-1.TRIAL REGISTRATIONClinicalTrials.gov NCT02296541.FUNDINGUS NIH grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069412, UL1 RR025758, P30 AI064518, UM1 AI100645, and UM1 AI144371, and Bill & Melinda Gates Foundation grant OPP52282.